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Peptide for triggering an immune reaction against tumor cells

a tumor cell and peptide technology, applied in the field of peptides, can solve the problems of mhc-unrestricted immune response efficiency, possible autoimmunity, and great disadvantage of mhc-unrestricted immune response in comparison to mhc-restricted on

Inactive Publication Date: 2009-05-05
IMMATICS BIOTECHNOLOGIES GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0022]Thus, this peptide offers the possibility of an effective tumor therapy, in which the suppression of an immune reaction against tumor cells often observed in tumor patients can be reversed.

Problems solved by technology

On the one hand, the problem of a possible autoimmunity can be reduced by avoiding an MHC-restricted immune response, on the other hand, the lower efficiency of an MHC-unrestricted immune response in comparison to an MHC-restricted one is a great disadvantage.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Induction of Antigen-Specific Cytotoxic T Cells by Using Peptides and Dendritic Cells

1.1 Providing Dendritic Cells

[0048]As e.g. described by Brossart, P., et al., Cancer Res 58 (1998), pages 732 ff.; first of all, mononuclear cells of peripheral blood were isolated from buffy coat preparations of heparinized blood of three healthy donators by Ficoll / Paque (Gibco-BRL, Grand Island, N.Y.) density-gradient centrifugation. The cells were seeded in cell culture bowls in RP10 medium. After two hours at 37° C., the cells that did not adhere were removed and the adhering blood monocytes were cultivated in RP10 medium that contained the following cytokine additives: human recombinant GM-CSF (Leukomax, Sandoz, 100 ng / ml), IL-4 (Genzyme, 1000 IU / ml), and TNF-α (Genzyme, 10 ng / ml). After seven days of cultivation, in the FACS analysis the cells showed a strong expression of the surface marker MHC class I and II, CD83, CD80, CD86, CD40 and CD54, characteristic of the phenotype of mature dendriti...

example 2

Lysis of Tumor Cells by MUC-1 Peptide Specific Cytotoxic T Cells

[0056]Different tumor cell lines that express either both HLA-A2 and MUC-1 or only one of the two cell surface molecules, respectively, as proven by FACS-analysis, were labeled with 51Cr, as described under 1.4 for T cells. After that, as also described under 1.4, the cells were incubated with cytotoxic T cells which were induced as described under 1.3.

[0057]Those T cells that were activated by using the peptides with the sequence SEQ ID NO: 1 or the sequence SEQ ID NO: 2 were able to lyse tumor cells of the lines MCF-7 (breast cancer cells), A-498 (kidney cell carcinoma cells) and MZ1774-RCC (kidney cell carcinoma cells) which express HLA-A2 and MUC-1. However, they were not able to lyse cells of the cell lines Croft (EBV immortalized B cells) which do not express MUC-1, as well as Caki-2 (kidney cell carcinoma cells), SK-OV-3 (ovary cancer cells) and K562 (pro-erythroblastic cells) which do not express HLA-A2.

[0058]Th...

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Abstract

The invention relates to a peptide for triggering an immune response to tumor cells. Said peptide has an optionally modified fragment of the protein that is encoded by the gene MUC-1. Said protein triggers an HLA-A2-restricted immune response.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This is a divisional application of U.S. Ser. No. 10 / 019,513 filed Aug. 6, 2002, issued as U.S. Pat. No. 7,087,712, issued Aug. 8, 2006, which is a U.S. National Stage application of International application No PCT / EP00 / 02699 filed Mar. 28, 2000 which claims priority from DE 19917195.5 filed Apr. 16, 1999.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates to a peptide that is derived from the MUC-1 gene, by which peptide a HLA-A2-restricted immune reaction against tumor cells can be triggered.[0004]2. Description of Related Art[0005]In an abstract to a lecture held on the 40. annual meeting of the American Society of Hematology, 1998, Brossart et al. show the possibility of deriving such a peptide from the MUC-1 gene, however, without mentioning the sequence of a peptide they tested or the localization of the sequence of a peptide that is not derived from the tandem repeat range of MUC-1.[0006]P...

Claims

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Application Information

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IPC IPC(8): A61K38/00A61K38/08A61K39/00A61K48/00A61P35/00A61P37/04C07K14/47C12N15/11
CPCC07K14/4727A61K39/00A61K48/00A61K2039/53A61P35/00A61P37/04A61K39/4611A61K39/46447
Inventor BROSSART, PETERSTEVANOVIC, STEFANBRUGGER, WOLFRAMKANZ, LOTHARRAMMENSEE, HANS GEORG
Owner IMMATICS BIOTECHNOLOGIES GMBH
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